This proposal requests funds for the purchase of an R-Axis IV++ detector, VariMax High resolution (HR) optical system, and Left port shutter configuration, plus the peripheral support instrumentation (including an X-stream cryo-cooling system), and necessary software required for this equipment to be integrated into the existing macromolecular X-ray diffraction data collection facility at the University of Florida (UF). This request to expand and improve the current facility (which contains a Rigaku RUH3R X-ray generator and Right port shutter configuration with Max-Flux (blue) Confocal optics and R-Axis IV++ Image plate system) comes from the following considerations. Primarily, adding a second detector to the Left port shutter with a VariMax HR optical system will enable realistic in-house diffraction quality screening on small crystals with large unit cells (such as viruses), by reducing exposures times to ~25% of that required on the current system and enabling crystallographic studies of viral samples under government agency regulations (such as USDA) that make transportation very difficult. The upgrade to an X-stream cryo-cooling system will also eliminate the need for insuring constant supplies of liquid nitrogen during long data collection runs. In addition, the usage of the current facility's Right port configuration is at near full capacity, due to the growing number of research groups employing structural biology tools as components of their biomedical research programs at UF. The installation of an additional R-Axis IV++ detector on the Left port of the current X-ray generator will effectively double the amount of available access time to the X-ray diffraction data collection facility for research aimed at macromolecular structure determinations at UF. This upgrade in technology will enable NIH PIs to expand their structure-function studies on biological systems (including ssDNA viruses, HIV proteases, metalloenzymes, and proteins associated with tumorgenesis, heart disease, the modulation of the immune system, and others) using X-ray crystallography. Significantly, these research efforts are directed towards the development of therapeutic treatments of human diseases and the control of pathogens in the form of small organic molecules, peptide inhibitors, vaccines, virus assembly disrupters, and gene therapy vectors. PUBLIC HEALTH RELEVANCE: This project proposes the expansion of the existing macromolecular X-ray diffraction data collection facility at the University of Florida (UF). The requested instrumentation will strengthen ongoing collaborative efforts between UF NIH investigators for whom molecular characterizations form the basis of their biomedical research programs. These projects are aimed at the development of therapeutic treatments of myriad of human disease and the control of pathogens in the form of small organic molecules, peptide inhibitors, vaccines, virus assembly disrupters, and gene therapy vectors.